Chiral Aliphatic Amines Research Articles

Integrating Au Catalysis and Engineered Amine Dehydrogenase for the Chemoenzymatic Synthesis of Chiral Aliphatic Amines

Integrating Au Catalysis and Engineered Amine Dehydrogenase for the Chemoenzymatic Synthesis of Chiral Aliphatic Amines

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

Chiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance.

Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines

To increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C–H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.

Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen

The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 % yield and 74 % ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)‐f‐binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user‐friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 % achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.

Novel heterogeneous ruthenium racemization catalyst for dynamic kinetic resolution of chiral aliphatic amines

Only few dynamic kinetic resolution (DKR) systems are known for chiral aliphatic amines due to the difficult racemization of these amines.

Liquid Chromatographic Enantiomeric Separation of Chiral Aliphatic Amines Using 2-Hydroxynaphthaldehyde as a Derivatizing Agent on Polysaccharide-Derived Chiral Stationary Phases

A new liquid chromatographic enantiomer separation of chiral amines as 2-hydroxynaphthaldimine derivatives on several coated and immobilized chiral stationary phases (CSPs) derived from polysaccharides is described. 2-Hydroxynaphthaldehyde was introduced as a derivatizing agent for the enantiomeric separation of chiral aliphatic amines under the normal phase conditions, and was found to both enhance detection sensitivity and provide suitable interaction sites for enantiodiscrimination. Cellulose-derived CSPs, in general, exhibited better enantiomeric separation than amylose-derived CSPs. Amongst the examined six covalently bonded and four coated-type CSPs, covalently bonded Chiralpak IC, which contains a cellulose-based chiral selector, showed the best enantioseparation. The method was applied to the determination of the enantiomeric purity of commercially available (R)- and (S)-leucinol. The enantiomeric impurities of the investigated analytes procured from two suppliers were found to be 0.06–1.20%. The developed analytical method was also validated in accordance with ICH guidelines and proved to be enantioselective, sensitive and effective for the enantiomeric separation of chiral aliphatic amines as 2-hydroxynaphthaldimine derivatives under ultraviolet detection.

Hydrolysis of Phosphonothioates with a Binaphthyl Group: P-Stereogenic O-Binaphthyl Phosphonothioic Acids and Their Use as Optically Active Ligands and Chiral Discriminating Agents.

The hydrolysis of phosphonothioates with a binaphthyl group afforded the first example of O-(2'-hydroxy)binaphthyl phosphonothioic acids in good to high yields and >95:5 diastereoselectivity. The reaction proceeds via an axis-to-center chirality-transfer reaction. The ability of these acids to act as chiral molecular auxiliaries was demonstrated by using them as optically active ligands for the asymmetric ethylation of benzaldehyde and as a chiral discriminating agent for chiral aliphatic amines.

A convenient and validated enantiomer separation of chiral aliphatic amines as nitrobenzoxadiazole derivatives on polysaccharide-derived chiral stationary phases under simultaneous ultraviolet and fluorescence detection.

A convenient method using a fluorogenic agent, 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl), was developed for enantiomer separation of chiral aliphatic amines including amino alcohols by normal high-performance liquid chromatography. The enantiomer separation of chiral aliphatic amines as NBD derivatives was performed on six covalently bonded and four coated-type polysaccharide-derived chiral stationary phases (CSPs) under simultaneous ultraviolet (UV) and fluorescence detection (FLD). Among the covalently bonded CSPs, Chiralpak IE showed the best enantiomer separation for most analytes. The other CSPs also showed good enantioselectivity except for Chiralpak IB. On the other hand, Chiralpak AD-H and Amylose-1 generally exhibited better enantiomer separation of NBD derivatized chiral amines among the coated CSPs. The developed analytical technique was also applied to determine the optical purity of commercially available (R)- and (S)-leucinol; the impurity was found to be 0.06%. The developed method was validated and proved to be an accurate, precise, sensitive, and selective method suitable for separation of chiral aliphatic amines as NBD derivatives under simultaneous UV and FLD.

Simultaneous chirality sensing of multiple amines by (19)F NMR.

The rapid detection and differentiation of chiral compounds is important to synthetic, medicinal, and biological chemistry. Palladium complexes with chiral pincer ligands are demonstrated to have utility in determining the chirality of various amines. The binding of enantiomeric amines induces distinct (19)F NMR shifts of the fluorine atoms appended on the ligand that defines a chiral environment around palladium. It is further demonstrated that this method has the ability to evaluate the enantiomeric composition and discriminate between enantiomers with chiral centers several carbons away from the binding site. The wide detection window provided by optimized chiral chemosensors allows the simultaneous identification of as many as 12 chiral amines. The extraordinary discriminating ability of this method is demonstrated by the resolution of chiral aliphatic amines that are difficult to separate using chiral chromatography.

ChemInform Abstract: Synthesis of Chiral Aliphatic Amines Through Asymmetric Hydrogenation.

AbstractThis method yields the hydrogenation products with excellent enantioselectivities.

Synthesis of Chiral Aliphatic Amines through Asymmetric Hydrogenation

Synthesis of Chiral Aliphatic Amines through Asymmetric Hydrogenation

Synthesis of Chiral Aliphatic Amines through Asymmetric Hydrogenation

Der direkte Weg: Ausgehend von leicht zugänglichen Ausgangsstoffen gelang die effiziente Synthese chiraler allylischer Amine und aliphatischer Amine mithilfe einer Rhodium-katalysierten asymmetrischen Hydrierung. Ein chirales Z-allylisches Amin wurde zum ersten Mal in einer von Rhodium/DuanPhos katalysierten asymmetrischen Hydrierung erhalten. TMS=Trimethylsilyl, cod=Cyclooctadien, TON=Umsatzzahl.

Enantioselective organocatalytic reductive amination of aliphatic ketones by benzothiazoline as hydrogen donor

The chiral phosphoric acid-catalyzed enantioselective reductive amination of aliphatic ketones with aromatic amines was successfully achieved by the use of benzothiazoline as the hydrogen donor. Corresponding chiral aliphatic amines were obtained with excellent enantioselectivities.

Synthesis, characterization and tumor cell growth inhibition of new trans platinum complexes with phosphane derivatives

We have reported the synthesis and characterization of two new trans platinum complexes in the phosphane series, where the phosphane ligand is triphenylphosphine [P(Ph) 3] and the group in the trans configuration is represented by chiral aliphatic amines, (racemic in complex 1 and S–NH 2CH 2CH(CH 3)CH 2CH 3 in complex 2). The anti-proliferative activity detected in tumor cells treated with the two new complexes is more pronounced when the aliphatic amine is racemic compared to the S-enantiomer. Moreover, for both compounds, the activity is fast after cell exposure and, unlike that of cisplatin, virtually independent of the duration of cell challenge.

A novel and efficient catalytic epoxidation of olefins with adducts derived from methyltrioxorhenium and chiral aliphatic amines

Nitrogen-based adducts derived from methyltrioxorhenium(VII) and chiral aliphatic amines have been synthesized and applied to the efficient catalytic epoxidation of olefins with urea hydrogen peroxide complex as the primary oxidant. These complexes retain their catalytic activity when microencapsulated in polystyrene. A moderate steroinduction was obtained in the epoxidation of prochiral olefins with complexes between methyltrioxorhenium and chiral trans-1,2-cyclohexyldiamine. The values of steroinduction were found to increase after the microencapsulation process.

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines

An efficient procedure has been developed for the diastereoselective synthesis of chiral aliphatic amines (diastereoisomeric excess >96%) from (1S)-N-(1-methylethylidene)-1-phenylethylamine, i.e., Schiff base derived from the simplest ketone (acetone) and (1S)-1-phenylethylamine. The procedure includes successive lithiation, alkylation, and reduction and is characterized by high regioselectivity in the formation of alkylated syn-Z-imines. Hydride reduction of the prochiral C=N bond in the latter gives mainly optically active aliphatic amines with R configuration. All reactions are performed as a one-pot process without isolation of intermediate products.

ChemInform Abstract: Resolution of Chiral Aliphatic and Arylalkyl Amines Using Immobilized Candida antarctica Lipase and Isolation of Their R‐ and S‐Enantiomers.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

RESOLUTION OF CHIRAL ALIPHATIC AND ARYLALKYL AMINES USING IMMOBILIZED CANDIDA ANTARCTICA LIPASE AND ISOLATION OF THEIR R- AND S-ENANTIOMERS

The resolution of chiral aliphatic and arylalkyl amines in high enantiomeric excess (up to 97.5% ee for the R-enantiomers and up to 99.9% ee for the S-enantiomers) and good yield (50–80%) using immobilized Candida antarctica lipase and ethyl acetate as acyl donor has been demonstrated. A second resolution on the R-amine increased the enantiomeric excess to more than 99.5% (up to 99.9%).